A major limitation in the pharmacological treatment of pulmonary arterial hypertension (PAH) is the lack of pulmonary vascular selectivity. Recent studies have identified a tissue-penetrating homing peptide, CARSKNKDC (CAR), which specifically homes to hypertensive pulmonary arteries but not to normal pulmonary vessels or other tissues. In an animal model of PAH, CAR peptide penetrated selectively into pulmonary hypertensive tissues and facilitated transport of co-administered PAH drugs into PAH lung tissues without the direct coupling of drug to the peptide as in conventional drug targeting.

The article describes how co-administered CAR selectively enhanced the pulmonary vascular effects of i.v. vasodilators in Sugen5416/hypoxia/normoxia-exposed PAH rats. Systemically administered CAR was predominantly detected in cells of remodeled pulmonary arteries. Intravenously co-administered CAR enhanced pulmonary, but not systemic, effects of the vasodilators, fasudil and imatinib, in PAH rats. CAR increased lung tissue imatinib concentration in isolated PAH lungs without increasing pulmonary vascular permeability. Sublingual CAR was also effective in selectively enhancing the pulmonary vasodilation by imatinib and sildenafil. These results suggest a new paradigm in the treatment of PAH, using an i.v./sublingual tissue-penetrating homing peptide to selectively augment pulmonary vascular effects of nonselective drugs without the potentially problematic conjugation process. CAR may be particularly useful as an add-on therapy to selectively enhance the pulmonary vascular efficacy of any ongoing drug treatment in patients with PAH.

CEO of Vascular BioSciences and study co-author, David Mann commented, “To our knowledge, this is the first orally available disease homing peptide that can selectively enhance the effects of co-administered drugs. Utilizing our CAR peptide in pulmonary hypertension has enabled us to demonstrate the feasibility of pulmonary selective therapy for this deadly pulmonary vascular disease. We are working hard to translate this important scientific discovery into clinically useful treatments for PAH patients.”